Normalcy and stability in the functional activity of living organisms and adaptation by the organism to newly developing situations is possible only with the stability of internal informational links within the organism, i.e., only with the informational stability of a living organism. The transfer of biological information and realization of its effects in living organisms has a complex multi-step character and includes vertical and horizontal links with a multitude of feedbacks at various stages.
Structurally, this complex multi-step biological information transfer can be subdivided into three basic levels: the generation and transfer of information; the recognition and decoding of initial information; and intracellular transformation of decoded information into a new external/outgoing signal. This information transfer is shown schematically in FIG. 1.
The generation of initial internal information takes place both within specialized organs synthesizing and secreting these or other biologically active substances and at the final stage of activity of the majority of cells in the living organism. The difference can consist only in the strength, character, concentration, and informational value of the information being generated. The information being generated represents only the first degree messengers. In other words, the carriers of the initial internal information are the various information substances modulating the final effects that are necessary at the output of the entire information chain.
The majority of biologically active substances, hormones etc. that have specific receptors in cells and target organs belong to this group of first degree messengers. Very often the place of synthesis and secretion of first degree messengers is at a considerable distance from the place of their final realization (cells and target organs). The most frequent (although not the only) way of transporting these substances to the cells and target organs is via the blood circulatory system. Another type of first degree messenger is the typical medicament, which due to its stereochemical structure, functions by acting upon various specific receptors in the cells and/or in target organs.
At the second level of biological information transfer is the recognition and decoding of initial information. This important element of information regulation involves the recognition of the first degree information substances and is carried out by strictly specific cell receptors. These receptors are typically located on the cell membrane (membrane receptors) or within the cells (cytosol or nuclear receptors), and included in their structure a polymeric molecule as a carrier of biological specificity. Any biomolecule specifically joining chemical compounds (ligand, agonist, antagonist, medication etc.) on the surface or within the cell and transforming received information into the cell's biological response can serve as a receptor. After the initial information is recognized by cellular receptors, it is processed by being decoded. Decoding of the incoming signal is possible due to conformational changes of the receptor structure and the activation of cell membrane and or intracellular decoding systems. Both decoding factors are strictly specific and are activated only after the complex of first degree messengers and cell receptors has been formed.
The effective realization of the process of this second level, as well as the regulation and stability thereof, depends to a great extent on the functional state and activity of transmembrane and intracellular conjunction agents, such as lipids, phospholipids, and other cell membrane structural components, etc.
At the third level, decoded information is transformed intracellularly into a new external/outgoing signal. This transformation of a molecular signal into a biochemical reaction consists in the synthesis of new information substances. It is important to point out that the intracellular information transfer has a more unified nature than the transfer of information at the previous two levels. More precisely, for each informational substance of the first degree and its corresponding receptor there is no specific agent responsible for the further transfer of intracellular information.
Thus, there are only a few universal ways of intracellular information transfer, which fall into one of the two following groups: extended notion of intracellular second degree messengers--signal transformation and transfer by means of cyclic nucleotides, inositol triphosphate-diacylglycerol line, Ca.sup.++ --calmodulin way, etc; or multifactor activators--translocation and intramolecular tie up of receptors with cell acceptors, temperature activation of first degree messenger-receptor complexes, ionic forces, intracellular cascade system, etc.
One can readily observe reduced diversity (but not intensity) of biological information transfer on the third level, which ensures the universal stability of the signal transfer and transformation structure on the intracellular level. All of this is expressed in the closed-system character of the intracellular information volume throughout the second degree messengers and their analogs.
Effective transformation of the decoded signal into the cell's biological response depends to a great extent on the functional activity of non-specific cell transmitters and trigger systems, particularly such as intracellular prostaglandins of various groups, i.e., PGE.sub.1&2, PGF.sub.1&2, PGA, PGB, prostacyclins, thromboxans, etc. Thus, normal functioning of intracellular information volume is ensured by the buffer concentration of intracellular prostaglandins. Intracellular information transformation and transfer leads to the activation of specific chromatin acceptor locations which initiate multiple specific effects, with transcription processes being initially modulated. The final effect of this complex chain of information transfer is stimulation/suppression of DNA synthesis, i.e., the final cellular response--information transformation from first degree messengers to a new cell output signal, which consists in the synthesis (generation) of new information substances. These newly-formed information substances, in their turn, influence the type and intensity of the signal which caused their stimulation/suppression by means of a feedback mechanism.
If structurally the transfer of biological information and the realization of its effects in living organisms is expressed in terms of three levels, it physically materializes itself in the form of informational blocks as shown in FIG. 2. It is important to point out that the transfer of biological information by blocks actually corresponds to the levels of information transfer.
The first informational block involves the formation of initial information, and includes two stages: synthesis and secretion of first degree messengers of natural origin, or introduction of artificial or non-naturally occurring substances; and the transporting of information substances to cells and target organs.
The second informational block involves the identification of information and includes two stages; strictly specific cell reception of the first degree messengers; and the decoding of a signal carried by the first degree messengers.
The third informational block involves the transformation of a molecular signal into a biochemical reaction and includes a set of intracellular transformers of decoded initial information and their transmitters into the cell final outgoing signal, which results in the synthesis of new information substances.
The informational stability of a living organism is thus affected by four factors: the intensity of influence (in terms of amount and concentration) of an entire group of antagonistically acting first degree informational substances (the first informational block); the presence (in terms of amount and activity) in cells and target organs of specific receptors for certain first degree information substances that initiate intracellular processes resulting in the synthesis of genetically determined new information substances (the second informational block); the functional state (in terms of amount and activity) of intracellular regulating mechanisms transforming the molecular signal into a biochemical reaction (the third informational block); and the genetic determination of the cell function.
When any of these factors are disturbed, a pathology results. Various pathologies have their basis in various stages of the biological information transfer. Thus, a common basis for therapy exists for all pathologies wherein this information transfer has been adversely affected.
Present methods of correction and/or treatment of the different pathologies (as well as skin dysfunctions) are aimed towards attempting to reconstruct the transfer of biological information both by means of interacting directly with the first degree messengers (peptides, steroids, lipids, etc.) and indirectly through the change in the activity and/or amount of the first degree information substances.
It is necessary to emphasize that such methods utilize the first degree informational substances in amounts greatly exceeding the endogenic production of these substances. For instance, prednisone, a commonly prescribed glucocorticosteroid hormone that is about 6-8 times more active that its endogenous analog hydrocortisone, is typically administered by injection in a dosage of 30 mg or orally, in a daily dosage of 12-16 mg. This is approximately equivalent to 40-60 days of the total production of the adrenal cortex gland (corticosuprarenal gland) of hydrocortisone. Taking into account the activity differential, one typical daily therapeutic dose of prednisone is similar to the amount produced by a normally functioning gland over a period of about ten months.
Additionally, the physiological and biochemical response from "therapeutic" and "physiological" dosages of bioactive substances are very different. Frequently, unusual and non-physiological effects are observed when the same bioactive substance is used in amounts exceeding the physiological level.
These current therapeutic practices are not without consequences since the administration of such amounts exceed the organism's normal endogenous production, and as a result causes the loss of the control of the organism's buffering mechanism. This results in a failure of restoration of the disrupted metabolism (disrupted transfer of biological information). The new non-physiological regulation quickly gets out of order, thereby creating more and more disruptions in the normal biological information transfer and making the organism's informational transfer unstable.
By referring to FIGS. 1 and 2, which diagram normal biological information transfer, it can be seen to what degree present therapeutic methods of treatment are inadequate and inefficient to ensure the information stability of the organism.
A most important aspect of any therapeutic method is the delivery of the active to the target receptor or cell of the organism. The delivery system utilized must provide stability for the active therein, while still allowing the absorption/delivery thereof. To effect useful therapy it is necessary that both requirements be met by the drug delivery system. Especially in the areas of topical and parenteral administration, it is critical to efficacy to provide a delivery system which crosses the cell membrane and allows the active agent or agents to exert their effects.
Stratum corneum, the outer layer of skin, is a multi-cellular membrane of flattened, metabolically active cells. In living organisms, the membrane is dynamic, and the transfer or non-transfer of various agents across this membrane is an important basis of both drug and cosmetic therapy. In order to provide useful therapeutic and cosmetic formulations, it is necessary to utilize a delivery system which is both compatible with the skin, i.e., non-irritating, and which will allow and even facilitate the transfer of the active agent, whether cosmetic or therapeutic, across the skin membrane. It is additionally necessary to utilize a delivery system in which the bioactive components are physically and chemically stable, yet still available for absorption.